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Öz DK, Ellik Z, Çoruh AG, Adıgüzel M, Gümüşsoy M, Kiremitci S, Kırımker EO, Gökcan H, Elhan AH, Balcı D, Savaş B, Erden A, İdilman R. Assessing hepatic steatosis by magnetic resonance in potential living liver donors. Diagn Interv Radiol 2024; 30:351-356. [PMID: 38737404 PMCID: PMC11589523 DOI: 10.4274/dir.2024.242697] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 04/17/2024] [Indexed: 05/14/2024]
Abstract
PURPOSE To determine the accuracy of magnetic resonance imaging-proton density fat fraction (MRI-PDFF) measurements for detecting liver fat content in potential living liver donors and to compare these results using liver biopsy findings. METHODS A total of 139 living liver donors (men/women: 83/56) who underwent MRI between January 2017 and September 2021 were included in this analysis retrospectively. The PDFFs were measured using both MR spectroscopy (MRS) and chemical shift-based MRI (CS-MRI) for each donor in a blinded manner. RESULTS Significant positive correlations were found between liver biopsy and MRS-PDFF and CS-MRI PDFF in terms of hepatic steatosis detection [r = 0.701, 95% confidence interval (CI): 0.604–0.798, r = 0.654, 95% CI: 0.544–0.765, P < 0.001, respectively). A weak level correlation was observed between liver biopsy, MRI methods, and vibration-controlled transient elastography attenuation parameters in 42 available donors. Based on receiver operating characteristic (ROC) analysis, MRS-PDFF and CS-MRI PDFF significantly distinguished >5% of histopathologically detected hepatic steatosis with an area under the ROC curve (AUC) of 0.837 ± 0.036 (P < 0.001, 95% CI: 0.766–0.907) and 0.810 ± 0.036 (P < 0.001, 95% CI: 0.739–0.881), respectively. The negative predictive values (NPVs) of MRS-PDFF and CS-MRI PDFF were 88.3% and 81.3%, respectively. In terms of distinguishing between clinically significant hepatic steatosis (≥10% on histopathology), the AUC of MRS-PDFF and CS-MRI were 0.871 ± 0.034 (P < 0.001 95% CI: 0.804–0.937) and 0.855 ± 0.036 (P < 0.001, 95% CI: 0.784–0.925), respectively. The NPVs of MRS-PDFF and CS-MRI were 99% and 92%, respectively. CONCLUSION The methods of MRS-PDFF and CS-MRI PDFF provide a non-invasive and accurate approach for assessing hepatic steatosis in potential living liver donor candidates. These MRI PDFF techniques present a promising clinical advantage in the preoperative evaluation of living liver donors by eliminating the requirement for invasive procedures like liver biopsy.
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Affiliation(s)
- Diğdem Kuru Öz
- Ankara University Faculty of Medicine, Department of Radiology, Ankara, Türkiye
| | - Zeynep Ellik
- Ankara University Faculty of Medicine, Department of Gastroenterology, Ankara, Türkiye
| | | | - Mehmet Adıgüzel
- Ankara University Faculty of Medicine, Department of Radiology, Ankara, Türkiye
| | - Mesut Gümüşsoy
- Ankara University Faculty of Medicine, Department of Gastroenterology, Ankara, Türkiye
| | - Saba Kiremitci
- Ankara University Faculty of Medicine, Department of Pathology, Ankara, Türkiye
| | - Elvan Onur Kırımker
- Ankara University Faculty of Medicine, Department of General Surgery, Ankara, Türkiye
| | - Hale Gökcan
- Ankara University Faculty of Medicine, Department of Gastroenterology, Ankara, Türkiye
| | - Atilla Halil Elhan
- Ankara University Faculty of Medicine, Department of Biostatistics, Ankara, Türkiye
| | - Deniz Balcı
- Bahçesehir University Faculty of Medicine, Department of General Surgery, İstanbul, Türkiye
| | - Berna Savaş
- Ankara University Faculty of Medicine, Department of Pathology, Ankara, Türkiye
| | - Ayşe Erden
- Ankara University Faculty of Medicine, Department of Radiology, Ankara, Türkiye
| | - Ramazan İdilman
- Ankara University Faculty of Medicine, Department of Gastroenterology, Ankara, Türkiye
- Ankara University Hepatology Institute, Ankara, Türkiye
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Qadri S, Vartiainen E, Lahelma M, Porthan K, Tang A, Idilman IS, Runge JH, Juuti A, Penttilä AK, Dabek J, Lehtimäki TE, Seppänen W, Arola J, Arkkila P, Stoker J, Karcaaltincaba M, Pavlides M, Loomba R, Sirlin CB, Tukiainen T, Yki-Järvinen H. Marked difference in liver fat measured by histology vs. magnetic resonance-proton density fat fraction: A meta-analysis. JHEP Rep 2024; 6:100928. [PMID: 38089550 PMCID: PMC10711480 DOI: 10.1016/j.jhepr.2023.100928] [Citation(s) in RCA: 18] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 08/17/2023] [Accepted: 09/12/2023] [Indexed: 12/22/2023] Open
Abstract
Background & Aims Pathologists quantify liver steatosis as the fraction of lipid droplet-containing hepatocytes out of all hepatocytes, whereas the magnetic resonance-determined proton density fat fraction (PDFF) reflects the tissue triacylglycerol concentration. We investigated the linearity, agreement, and correspondence thresholds between histological steatosis and PDFF across the full clinical spectrum of liver fat content associated with non-alcoholic fatty liver disease. Methods Using individual patient-level measurements, we conducted a systematic review and meta-analysis of studies comparing histological steatosis with PDFF determined by magnetic resonance spectroscopy or imaging in adults with suspected non-alcoholic fatty liver disease. Linearity was assessed by meta-analysis of correlation coefficients and by linear mixed modelling of pooled data, agreement by Bland-Altman analysis, and thresholds by receiver operating characteristic analysis. To explain observed differences between the methods, we used RNA-seq to determine the fraction of hepatocytes in human liver biopsies. Results Eligible studies numbered 9 (N = 597). The relationship between PDFF and histology was predominantly linear (r = 0.85 [95% CI, 0.80-0.89]), and their values approximately coincided at 5% steatosis. Above 5% and towards higher levels of steatosis, absolute values of the methods diverged markedly, with histology exceeding PDFF by up to 3.4-fold. On average, 100% histological steatosis corresponded to a PDFF of 33.0% (29.5-36.7%). Targeting at a specificity of 90%, optimal PDFF thresholds to predict histological steatosis grades were ≥5.75% for ≥S1, ≥15.50% for ≥S2, and ≥21.35% for S3. Hepatocytes comprised 58 ± 5% of liver cells, which may partly explain the lower values of PDFF vs. histology. Conclusions Histological steatosis and PDFF have non-perfect linearity and fundamentally different scales of measurement. Liver fat values obtained using these methods may be rendered comparable by conversion equations or threshold values. Impact and implications Magnetic resonance-proton density fat fraction (PDFF) is increasingly being used to measure liver fat in place of the invasive liver biopsy. Understanding the relationship between PDFF and histological steatosis fraction is important for preventing misjudgement of clinical status or treatment effects in patient care. Our analysis revealed that histological steatosis fraction is often significantly higher than PDFF, and their association varies across the spectrum of fatty liver severity. These findings are particularly important for physicians and clinical researchers, who may use these data to interpret PDFF measurements in the context of histologically evaluated liver fat content.
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Affiliation(s)
- Sami Qadri
- Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Minerva Foundation Institute for Medical Research, Helsinki, Finland
| | - Emilia Vartiainen
- Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki, Finland
| | - Mari Lahelma
- Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Minerva Foundation Institute for Medical Research, Helsinki, Finland
| | - Kimmo Porthan
- Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Minerva Foundation Institute for Medical Research, Helsinki, Finland
| | - An Tang
- Department of Radiology, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, QC, Canada
| | - Ilkay S. Idilman
- Liver Imaging Team, Hacettepe University, School of Medicine, Department of Radiology, Ankara, Turkey
| | - Jurgen H. Runge
- Department of Radiology and Nuclear Medicine, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands
| | - Anne Juuti
- Department of Gastrointestinal Surgery, Abdominal Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Anne K. Penttilä
- Department of Gastrointestinal Surgery, Abdominal Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Juhani Dabek
- Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Minerva Foundation Institute for Medical Research, Helsinki, Finland
| | - Tiina E. Lehtimäki
- HUS Medical Imaging Center, Helsinki University Hospital, Helsinki, Finland
| | - Wenla Seppänen
- HUS Medical Imaging Center, Helsinki University Hospital, Helsinki, Finland
| | - Johanna Arola
- Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Perttu Arkkila
- Department of Gastroenterology, Abdominal Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Jaap Stoker
- Department of Radiology and Nuclear Medicine, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands
| | - Musturay Karcaaltincaba
- Liver Imaging Team, Hacettepe University, School of Medicine, Department of Radiology, Ankara, Turkey
| | - Michael Pavlides
- Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Rohit Loomba
- NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, USA
| | - Claude B. Sirlin
- Liver Imaging Group, Department of Radiology, University of California San Diego, La Jolla, CA, USA
| | - Taru Tukiainen
- Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki, Finland
| | - Hannele Yki-Järvinen
- Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Minerva Foundation Institute for Medical Research, Helsinki, Finland
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Rajesh S, Arunachalam VK, Periaswamy G, Kalyan G, Renganathan R, SM G, Cherian M. Accuracy of Evaluation of Fatty Liver with Third-Generation Unenhanced Dual-Energy CT and MRI: Prospective Comparison with MR Spectroscopy. JOURNAL OF GASTROINTESTINAL AND ABDOMINAL RADIOLOGY 2023. [DOI: 10.1055/s-0043-1763483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/31/2023] Open
Abstract
Abstract
Background and Objectives The purpose of this study is to evaluate and establish the accuracy of noninvasive methods, including third-generation dual-source dual-energy computed tomography (DECT) and proton density fat (PDF) fraction on magnetic resonance imaging (MRI) using three-dimensional multiecho multipoint chemical shift-encoded spoiled gradient echo (q-Dixon) sequence in the quantification of hepatic steatosis; with H1-MR spectroscopy (MRS) as the reference standard.
Materials and Methods A total of 47 patients were included in this prospective study. We studied the accuracy of fatty liver detection using third-generation DECT using mixed set images (MSIs), virtual monochromatic images (VMIs), and MRI q-Dixon. The results were compared with H1-MRS. Data were analyzed using linear regression for each technique compared with MRS.
Results Our study's correlation and linear regression analysis showed a good correlation between PDF values obtained by H1-MRS and MR q-Dixon methods (r = 0.821, r
2 = 0.674, p < 0.001). On MSI, H1-MRS showed a low correlation with average liver attenuation (r
2 = 0.379, p < 0.001) and a moderate correlation with liver attenuation index (r
2 = 0.508, p < 0.001) noted. There was a moderate correlation between H1-MRS and average liver attenuation and liver attenuation index on VMI at 80 to 120 keV with r
2 = 0.434, p < 0.001, and r
2 = 0.485, p < 0.001, respectively.
Conclusion MRI q-Dixon is the method of choice for evaluating fat quantification in the absence of H1 MRS. Among DECT images, VMI is valuable in the evaluation of hepatic fat as compared with the mixed set of images.
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Nidoni R, Dey R, Agarwal S, Hirata Y, Vijayashanker A, Ghimire R, Sreejith S, Imbaraj B, Pandey Y, Goyal S, Pande V, Nasa V, Singh S, Gupta S. Single center experience of 3000 consecutive living donor hepatectomies. JOURNAL OF LIVER TRANSPLANTATION 2022. [DOI: 10.1016/j.liver.2022.100107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
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Li YW, Jiao Y, Chen N, Gao Q, Chen YK, Zhang YF, Wen QP, Zhang ZM. How to select the quantitative magnetic resonance technique for subjects with fatty liver: A systematic review. World J Clin Cases 2022; 10:8906-8921. [PMID: 36157636 PMCID: PMC9477046 DOI: 10.12998/wjcc.v10.i25.8906] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 05/25/2022] [Accepted: 07/22/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Early quantitative assessment of liver fat content is essential for patients with fatty liver disease. Mounting evidence has shown that magnetic resonance (MR) technique has high accuracy in the quantitative analysis of fatty liver, and is suitable for monitoring the therapeutic effect on fatty liver. However, many packaging methods and postprocessing functions have puzzled radiologists in clinical applications. Therefore, selecting a quantitative MR imaging technique for patients with fatty liver disease remains challenging. AIM To provide information for the proper selection of commonly used quantitative MR techniques to quantify fatty liver. METHODS We completed a systematic literature review of quantitative MR techniques for detecting fatty liver, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. Studies were retrieved from PubMed, Embase, and Cochrane Library databases, and their quality was assessed using the Quality Assessment of Diagnostic Studies criteria. The Reference Citation Analysis database (https:// www.referencecitationanalysis.com) was used to analyze citation of articles which were included in this review. RESULTS Forty studies were included for spectroscopy, two-point Dixon imaging, and multiple-point Dixon imaging comparing liver biopsy to other imaging methods. The advantages and disadvantages of each of the three techniques and their clinical diagnostic performances were analyzed. CONCLUSION The proton density fat fraction derived from multiple-point Dixon imaging is a noninvasive method for accurate quantitative measurement of hepatic fat content in the diagnosis and monitoring of fatty liver progression.
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Affiliation(s)
- You-Wei Li
- Department of Radiology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, China
| | - Yang Jiao
- Department of Rehabilitation Psychology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, China
| | - Na Chen
- Department of Otorhinolaryngology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, China
| | - Qiang Gao
- Department of Gastroenterology and Hepatology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, China
| | - Yu-Kun Chen
- Department of Radiology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, China
| | - Yuan-Fang Zhang
- Department of Radiology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, China
| | - Qi-Ping Wen
- Department of Radiology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, China
| | - Zong-Ming Zhang
- Department of General Surgery, Beijing Electric Power Hospital, State Grid Corporation of China, Capital Medical University, Beijing 100073, China
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Seifeldein GS, Hassan EA, Imam HM, Makboul R, Idriss NK, Gaber MA, Elkady RM. Quantitative MDCT and MRI assessment of hepatic steatosis in genotype 4 chronic hepatitis C patients with fibrosis. THE EGYPTIAN JOURNAL OF RADIOLOGY AND NUCLEAR MEDICINE 2021. [DOI: 10.1186/s43055-021-00590-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Hepatic steatosis has been shown to worsen the course of liver disease in chronic hepatitis C (CHC) patients, and it may reduce the efficacy of antiviral therapy and accelerate disease progression. In this cross-sectional study, we aimed to evaluate the role of multidetector computed tomography and magnetic resonance imaging (MRI) in the quantitative assessment and grading of hepatic steatosis to evaluate the association between hepatic steatosis and fibrosis in Egyptian genotype 4-CHC (G4-CHC) patients.
Results
Histopathological hepatic steatosis was found in 70.3% of 155 patients. No correlation was found between the CT ratio and pathological hepatic steatosis. Proton density fat fraction, T1-fat fraction, and fat percentage correlated with histological steatosis grading (r = 0.953, p < 0.001; r = 0.380, p = 0.027 and r = 0.384, p = 0.025, respectively). An agreement between steatosis grading by histology and 1H-MRS was found in 74.2% of patients. Compared to other MRI modalities, proton density fat fraction had the highest area under the receiver operating characteristic curve (AUC), with 0.910, 0.931, and 0.975 for mild, moderate, and severe steatosis, respectively. The cutoff with the best ability to predict steatosis was > 4.95 for a proton density fat fraction (AUC = 0.958) with 95.8% sensitivity, 90% specificity, 78.5% positive predictive value, and 96.1% negative predictive value.
Conclusion
1H-MRS had good diagnostic performance in predicting hepatic steatosis in G4-CHC patients, and hence, it may offer a useful noninvasive quantitative modality for grading steatosis with clinical applicability, especially in those where a liver biopsy cannot be done.
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Chaudhary A, Sood G, Kumar N, Chauhan C, Yadav DPS, Kasana V, Arora R, Gangwani G. Validation of Accuracy of Non-Invasive Imaging Methods (Magnetic Resonance Imaging (MRI) Fat Fraction Calculation and Computed Tomography (CT) Liver Attenuation Index) for Hepatic Graft Fat Quantification in Living Liver Transplant Donors. Ann Transplant 2021; 26:e933801. [PMID: 34824190 PMCID: PMC8630986 DOI: 10.12659/aot.933801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Diagnosis of significant hepatic graft steatosis remains vital for success of any transplant program as it has an impact on donor morbidity and recipient survival. Even histopathological quantification faces limitations. The present study compared the diagnostic accuracy of CT-LAI and MRI fat fraction imaging with histopathological analysis for donor graft parenchymal fat quantification. MATERIAL AND METHODS CT-LAI and MR-FF values and histopathological fat quantification results of 273 patients were identified from electronic records of the author's institutes from September 2015 to April 2020. Data analysis was done using SPSS version 21.0. RESULTS Most participants were young with nearly equal sex distribution and significant number of overweight and obese patients. Moderate agreement and significant positive correlation were found between MR fat fraction (%) and biopsy-macrosteatosis (%). Diagnostic accuracy and negative predictive value of MRI for fat fraction calculation was high (95.24% and 98.07% for fat fraction of 10% threshold, respectively), and it further improved for fat fraction threshold of 15%. CONCLUSIONS MRI-based fat quantification calculation displayed near-perfect negative predictive values and very high diagnostic accuracy, suggesting that it can obviate the need for biopsy in patients with graft fat percentage <10% on MRI.
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Affiliation(s)
- Abhideep Chaudhary
- Department of HPB Surgery and Liver Transplantation, B L Kapur Super Speciality Hospital, New Delhi, India
| | - Gaurav Sood
- Department of HPB Surgery and Liver Transplantation, B L Kapur Super Speciality Hospital, New Delhi, India
| | - Niteen Kumar
- Department of HPB Surgery and Liver Transplantation, B L Kapur Super Speciality Hospital, New Delhi, India
| | | | | | - Vivek Kasana
- Department of Radiodiagnosis, B L Kapur Super Speciality Hospital, New Delhi, India
| | - Raman Arora
- Department of Lab Medicine, Jaypee Hospital, Noida, India
| | - Gaurav Gangwani
- Department of Interventional Radiology, Bhaktivedanta Hospital, Thane, India
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Burian M, Hajek M, Sedivy P, Mikova I, Trunecka P, Dezortova M. Lipid Profile and Hepatic Fat Content Measured by 1H MR Spectroscopy in Patients before and after Liver Transplantation. Metabolites 2021; 11:metabo11090625. [PMID: 34564441 PMCID: PMC8469029 DOI: 10.3390/metabo11090625] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Revised: 09/09/2021] [Accepted: 09/10/2021] [Indexed: 12/11/2022] Open
Abstract
Increased hepatic fat content (HFC) is a hallmark of non-alcoholic fatty liver (NAFL) disease, a common condition in liver transplant recipients. Proton MR spectroscopy (1H MRS) and MR imaging-based proton density fat fraction as the only diagnosis modality enable precise non-invasive measurement of HFC and, also, fatty acid profiles in vivo. Using 1H MRS at 3T, we examined 47 liver transplantation candidates and 101 liver graft recipients. A point-resolved spectroscopy sequence was used to calculate the steatosis grade along with the saturated, unsaturated and polyunsaturated fractions of fatty acids in the liver. The steatosis grade measured by MRS was compared with the histological steatosis grade. HFC, represented by fat fraction values, is adept at distinguishing non-alcoholic steatohepatitis (NASH), NAFL and non-steatotic liver transplant patients. Relative hepatic lipid saturation increases while unsaturation decreases in response to increased HFC. Additionally, relative hepatic lipid saturation increases while unsaturation and polyunsaturation both decrease in liver recipients with histologically proven post-transplant NASH or NAFL compared to non-steatotic patients. HFC, measured by in vivo 1H MRS, correlated well with histological results. 1H MRS is a simple and fast method for in vivo analysis of HFC and its composition. It provides non-invasive support for NAFL and NASH diagnoses.
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Affiliation(s)
- Martin Burian
- MR-Unit, Department of Diagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech Republic; (M.B.); (M.H.); (P.S.)
| | - Milan Hajek
- MR-Unit, Department of Diagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech Republic; (M.B.); (M.H.); (P.S.)
| | - Petr Sedivy
- MR-Unit, Department of Diagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech Republic; (M.B.); (M.H.); (P.S.)
| | - Irena Mikova
- Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech Republic; (I.M.); (P.T.)
| | - Pavel Trunecka
- Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech Republic; (I.M.); (P.T.)
| | - Monika Dezortova
- MR-Unit, Department of Diagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech Republic; (M.B.); (M.H.); (P.S.)
- Correspondence: ; Tel.: +420-236055245
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Stanislawski MA, Shaw J, Litkowski E, Lange EM, Perng W, Dabelea D, Lange LA. Genetic Risk for Hepatic Fat among an Ethnically Diverse Cohort of Youth: The Exploring Perinatal Outcomes among Children Study. J Pediatr 2020; 220:146-153.e2. [PMID: 32143931 PMCID: PMC8148653 DOI: 10.1016/j.jpeds.2020.01.031] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Revised: 12/18/2019] [Accepted: 01/13/2020] [Indexed: 12/15/2022]
Abstract
OBJECTIVE To assess the importance of genetic and nongenetic risk factors contributing to hepatic fat accumulation in a multiethnic population of youth. STUDY DESIGN We investigated the relationship between genetic factors and hepatic fat fraction (HFF) in 347 children aged 12.5-19.5 years. We examined 5 single nucleotide polymorphisms previously associated with HFF and a weighted genetic risk score (GRS) and examined how these associations varied with ethnicity (Hispanic vs non-Hispanic white) and body mass index (BMI) category. We also compared how much variation in HFF was explained by genetic factors vs cardiometabolic factors (BMI z-score and the Homeostasis Model of Insulin Resistance) or diet. RESULTS PNPLA3 rs738409 and the GRS were each associated with HFF among Hispanic (β = 0.39; 95% CI, 0.16-0.62; P = .001; and β = 0.20; 95% CI, 0.05-0.34; P = .007, respectively) but not non-Hispanic white (β = 0.04; 95% CI, -0.18 to 0.26; P = .696; and β = 0.03; 95% CI, -0.09 to 0.14; P = .651, respectively) youth. Cardiometabolic risk factors explained more of the variation in HFF than genetic risk factors among non-lean Hispanic individuals (27.2% for cardiometabolic markers vs 6.4% for rs738409 and 4.3% for the GRS), and genetic risk factors were more important among lean individuals (2.7% for cardiometabolic markers vs 12.6% for rs738409 and 4.4% for the GRS). CONCLUSIONS Poor cardiometabolic health may be more important than genetic factors when predicting HFF in overweight and obese young populations. Genetic risk is an important contributor to pediatric HFF among lean Hispanics, but further studies are necessary to elucidate the strength of the association between genetic risk and HFF in non-Hispanic white youth.
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Affiliation(s)
- Maggie A Stanislawski
- Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO; Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO.
| | - Jessica Shaw
- Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO; Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO
| | - Elizabeth Litkowski
- Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO; Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO
| | - Ethan M Lange
- Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO; Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO
| | - Wei Perng
- Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO; Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO
| | - Dana Dabelea
- Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO; Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO; Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO
| | - Leslie A Lange
- Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO; Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO; Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO
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Shi Z, Xing H, Qi C, Fang M, Fu J, Zhang X. Chinese tree shrews as a primate experimental animal eligible for the study of alcoholic liver disease: characterization and confirmation by MRI. Exp Anim 2019; 69:110-118. [PMID: 31554748 PMCID: PMC7004808 DOI: 10.1538/expanim.19-0073] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
There has been a lack of suitable fatty liver models and characterization techniques for
histopathological evaluation of alcoholic fatty liver (AFL). This work aimed to exploit an
magnetic resonance imaging (MRI) technique for characterizing an alcohol-induced fatty
liver model established in tree shrews (Tupaia belangeri chinese). The
animals were treated with 15% alcohol for two weeks instead of drinking water to induce
AFL. Blood alanine aminotransferase (ALT), aspartate aminotransferase (AST), alcohol, and
liver malondialdehyde (MDA) concentrations were determined, and the histopathology of the
liver was checked by hematoxylin & eosin (HE) and Oil red O staining on day 0 and on
the 4th, 7th and 14th days after alcohol feeding. MRI was used to trace the
histopathological changes in the liver of tree shrews in real time. Compared with the
control group, the levels of ALT, AST, and MDA significantly increased in the
alcohol-induced group and were positively correlated with the induction time. HE and Oil
red O staining revealed that a moderate fatty lesion occurred in the liver on the 4th day
and that a serious AFL was successfully induced on the 14th day. MRI further confirmed the
formation of AFL. MRI, as noninvasive examination technique, provides an alternative tool
for accurate characterization of AFL in live subjects. It is comparable to HE or Oil red O
staining for histopathological examination, but is more suitable by virtue of its high
flexibility and compliance. The AFL model of tree shrews combined with MRI
characterization can work as a platform for studying fatty liver diseases and medications
for their treatment.
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Affiliation(s)
- Zhihai Shi
- Institute of Animal Husbandry and Veterinary, Henan Academy of Agricultural Sciences, 116 Huayuan Road, Zhengzhou, Henan Province 450008, P.R. China
| | - Huijie Xing
- Institute of Laboratory Animals, Jinan University, 601 West Huangpu Avenue, Guangzhou, Guangdong Province 510632, P.R. China
| | - Chunli Qi
- Institute of Laboratory Animals, Jinan University, 601 West Huangpu Avenue, Guangzhou, Guangdong Province 510632, P.R. China
| | - Meixia Fang
- Institute of Laboratory Animals, Jinan University, 601 West Huangpu Avenue, Guangzhou, Guangdong Province 510632, P.R. China
| | - Jiangnan Fu
- Institute of Laboratory Animals, Jinan University, 601 West Huangpu Avenue, Guangzhou, Guangdong Province 510632, P.R. China
| | - Xingwang Zhang
- Department of Pharmaceutics, School of Pharmacy, Jinan University, 601 West Huangpu Avenue, Guangzhou, Guangdong Province 510632, P.R. China
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11
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Stanislawski MA, Lozupone CA, Wagner BD, Eggesbø M, Sontag MK, Nusbacher N, Martinez M, Dabelea D. Gut microbiota in adolescents and the association with fatty liver: the EPOCH study. Pediatr Res 2018; 84. [PMID: 29538359 PMCID: PMC6185796 DOI: 10.1038/pr.2018.32] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Recent evidence supports that the gut microbiota may be involved in the pathophysiology of non-alcoholic fatty liver disease (NAFLD), and may also offer avenues for treatment or prevention. METHODS We investigated the associations among gut microbiota, diet, and hepatic fat fraction (HFF) in 107 adolescents. Magnetic resonance imaging (MRI) was used to assess HFF, and 16S rRNA gene sequencing was performed on collected fecal samples. Dietary intake was assessed using Food Frequency Questionnaires. We examined the association between gut microbiota alpha diversity and HFF, and assessed the predictive accuracy for HFF of (1) taxonomic composition, (2) dietary intake, (3) demographic and comorbid conditions, and (4) the combination of these. RESULTS Lower alpha diversity was associated with higher HFF (β=-0.19, 95% confidence interval (CI) -0.36, -0.02). The selected taxa explained 17.7% (95% CI: 16.0-19.4%) of the variation in HFF. The combination of two of these taxa, Bilophila and Paraprevotella, with dietary intake of monounsaturated fatty acids and BMI z-scores explained 32.0% (95% CI: 30.3-33.6%) of the variation in HFF. CONCLUSION The gut microbiota is associated with HFF in adolescents and may be useful to help identify youth who would be amenable to gut microbiota-based interventions.
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Affiliation(s)
| | | | | | - Merete Eggesbø
- Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway
| | | | | | | | - Dana Dabelea
- Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado, USA.
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12
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13
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Kim SR, Yi HJ, Lee YN, Park JY, Hoffman RM, Okano T, Shim IK, Kim SC. Engineered mesenchymal stem-cell-sheets patches prevents postoperative pancreatic leakage in a rat model. Sci Rep 2018; 8:360. [PMID: 29321630 PMCID: PMC5762914 DOI: 10.1038/s41598-017-18490-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2017] [Accepted: 12/12/2017] [Indexed: 12/22/2022] Open
Abstract
Post-operative pancreatic fistula (POPF) following pancreatic resection is a life-threatening surgical complication. Cell sheets were prepared and harvested using temperature-responsive culture dishes and transplanted as patches to seal POPF. Two different mesenchymal stem cell (MSC) sheets were compared in terms of the preventative ability for pancreatic leakage in a rat model. Both rat adipose-derived stem cell (rADSC) and bone marrow-derived stem cell (rBMSC) sheets were transplanted. Those rADSC and rBMSC sheets are created without enzymes and thus maintained their cell-cell junctions and adhesion proteins with intact fibronectin on the basal side, as well as characteristics of MSCs. The rats with post-pancreatectomy rADSC- or rBMSC-sheet patches had significantly decreased abdominal fluid leakage compared with the control group, demonstrated by MR image analysis and measurement of the volume of abdominal fluid. Amylase level was significantly lower in the rats with rADSC-sheet and rBMSC-sheet patches compared with the control groups. The rADSC sheet patches had increased adhesive and immune-cytokine profiles (ICAM-1, L-selectin, TIMP-1), and the rBMSC sheets had reduced immune reactions compared to the control. This is first project looking at the feasibility of tissue engineering therapy using MSC-sheets as tissue patches preventing leakage of abdominal fluid caused by POPF.
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Affiliation(s)
- Seong-Ryong Kim
- Department of Surgery, Division of HBP and Liver Transplantation, Korea University Anam Hospital, Seoul, Korea
| | - Hye-Jin Yi
- Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yu Na Lee
- Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ji Yoon Park
- Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Department of Chemistry, Wesleyan University, Connecticut, United States
| | - Robert M Hoffman
- Department of Surgery, University of California, San Diego, CA, USA
- AntiCancer Inc., San Diego, CA, USA
| | - Teruo Okano
- Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, Japan
| | - In Kyong Shim
- Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
| | - Song Cheol Kim
- Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
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14
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Cheng X, Blake GM, Brown JK, Guo Z, Zhou J, Wang F, Yang L, Wang X, Xu L. The measurement of liver fat from single-energy quantitative computed tomography scans. Quant Imaging Med Surg 2017; 7:281-291. [PMID: 28811994 DOI: 10.21037/qims.2017.05.06] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
BACKGROUND Studies of soft tissue composition using computed tomography (CT) scans are often semi-quantitative and based on Hounsfield units (HU) measurements that have not been calibrated with a quantitative CT (QCT) phantom. We describe a study to establish the water (H2O) and dipotassium hydrogen phosphate (K2HPO4) basis set equivalent densities of fat and fat-free liver tissue. With this information liver fat can be accurately measured from any abdominal CT scan calibrated with a suitable phantom. METHODS Liver fat content was measured by comparing single-energy QCT (SEQCT) HU measurements of the liver with predicted HU values for fat and fat-free liver tissue calculated from their H2O and K2HPO4 equivalent densities and calibration data from a QCT phantom. The equivalent densities of fat were derived from a listing of its constituent fatty acids, and those of fat-free liver tissue from a dual-energy QCT (DEQCT) study performed in 14 healthy Chinese subjects. This information was used to calculate liver fat from abdominal SEQCT scans performed in a further 541 healthy Chinese subjects (mean age 62 years; range, 31-95 years) enrolled in the Prospective Urban Rural Epidemiology (PURE) Study. RESULTS The equivalent densities of fat were 941.75 mg/cm3 H2O and -43.72 mg/cm3 K2HPO4, and for fat-free liver tissue 1,040.13 mg/cm3 H2O and 21.34 mg/cm3 K2HPO4. Liver fat in the 14 subjects in the DEQCT study varied from 0-17.9% [median: 4.5%; interquartile range (IQR): 3.0-7.9%]. Liver fat in the 541 PURE study subjects varied from -0.3-29.9% (median: 4.9%; IQR: 3.4-6.9%). CONCLUSIONS We have established H2O and K2HPO4 equivalent densities for fat and fat-free liver tissue that allow a measurement of liver fat to be obtained from any abdominal CT scan acquired with a QCT phantom. Although radiation dose considerations preclude the routine use of QCT to measure liver fat, the method described here facilitates its measurement in patients having CT scans performed for other purposes. Further studies comparing the results with magnetic resonance (MR) measurements of liver fat are required to validate the method as a useful clinical tool.
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Affiliation(s)
- Xiaoguang Cheng
- Department of Radiology, Beijing Jishuitan Hospital, Beijing 100035, China
| | - Glen M Blake
- Biomedical Engineering Department, King's College London, Strand, London WC2R 2LS, UK
| | | | - Zhe Guo
- Department of Radiology, Beijing Jishuitan Hospital, Beijing 100035, China
| | - Jun Zhou
- Department of Radiology, Shenyang No.4 Hospital, Shenyang 110082, China
| | - Fengzhe Wang
- Department of Radiology, Shenyang No.4 Hospital, Shenyang 110082, China
| | - Liqiang Yang
- Department of Radiology, the General Hospital of CNPC in Jilin City, Jilin 132021, China
| | - Xiaohong Wang
- Department of Radiology, the General Hospital of CNPC in Jilin City, Jilin 132021, China
| | - Li Xu
- Department of Radiology, Beijing Jishuitan Hospital, Beijing 100035, China
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